Physiologically Inspired Mucin Coated Escherichia coli Nissle 1917 Enhances Biotherapy by Regulating the Pathological Microenvironment to Improve Intestinal Colonization

Abstract

The delivery of probiotics to the microbiota is a promising method to prevent and treat diseases. However, oral probiotics will suffer from gastrointestinal insults, especially the pathological microenvironment of inflammatory diseases such as reactive oxygen species (ROS) and the exhausted mucus layer, which can limit their survival and colonization in the intestinal tract. Inspired by the fact that probiotics colonized and grew in the mucus layer under physiological conditions, we developed a strategy for a super probiotic (EcN@TA-Ca²⁺@Mucin) coated with tannic acid and mucin via layer-by-layer technology. We demonstrated that mucin endows probiotics with superior resistance to the harsh environment of the gastrointestinal tract and with strong adhesiveness to the intestine through its interaction with mucus, which enhanced colonization and growth of probiotics in the mucus layer without removing the coating. Moreover, EcN@TA-Ca²⁺@Mucin can distinctly down-regulate inflammation with ROS scavenging and reduce the side effects of bacterial translocation in inflammatory bowel diseases, increasing the abundance and diversity of the gut microflora. We envision that it is a powerful platform to improve the colonization of probiotics by regulating the pathological microenvironment, which is expected to provide an important perspective for applying the intestinal colonization of probiotics to treat a variety of diseases.

Keywords: intestinal adhesion; mucin coating; oral probiotics delivery; pathological microenvironment; probiotic colonization.